Transcranial Doppler in Multiple Sclerosis

NCT ID: NCT02389426

Last Updated: 2015-04-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-12-31

Study Completion Date

2015-04-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The aim of this study is to investigate the potential of Transcranial doppler (TCD) and Near-Infrared Spectroscopy (NIRS), more simple and non-invasive bedside methods than magnetic resonance imaging (MRI), to evaluate changes in the cerebral circulation between patients with MS and control subjects.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

MS is a poorly understood chronic disease of the central nervous system characterized by focal inflammatory demyelinating lesions and diffuse axonal degeneration. Recent magnetic resonance imaging (MRI) studies demonstrated a widespread decrease in cerebral perfusion - expressed as cerebral blood flow (CBF) - throughout the normal-appearing white matter of patients with MS, which seems not just to be secondary to axonal degeneration with reduced metabolic demands, but in contrast may actively contribute to MS pathology.

Reduced CBF in MS is mediated by elevated levels of the potent vasoconstrictive agent endothelin-1 (ET-1), likely released in the cerebral circulation by reactive astrocytes, and can reversed with administration of the ET-1 antagonist bosentan.

Phase-contrast MRI recently demonstrated reduced cervical arterial blood flow velocities to the brain in patients MS as compared to control subjects. The aim of this study is to investigate the potential of TCD and NIRS, more simple and non-invasive bedside method, to evaluate changes in the cerebral circulation between patients with MS and control subjects.

A baseline TCD examination will be performed in each subject (MS patients and controls) over the temporal bone window on both sides. Middle cerebral artery wave forms will be identified at a depth range of 40-60 mm and a stable forward waveform with good intensity will be selected. TCD probes (2 MHz) will be mounted by a head frame to ensure a constant angle of insonation throughout the procedure. Mean, peak-systolic and end-diastolic blood flow velocities can be directly recorded from the machine. Blood pressure (BP) and heart rate will be measured with a finger plethysmograph. The cuff will be applied to the middle finger of the left hand, first placed at the heart level to calibrate the system, afterwards the hand is placed next to the subject in rest. Near-infrared spectroscopy will be performed to measure cerebral frontal lobe oxygen saturation. NIRS is performed with two large sensors, attached on patient's forehead bilaterally. In bright environments, a light-blocker to cover the sensors will be used to reduce interference from ambient light. Continuously NIRS recording with a 2s interval refreshment. Measurements will be done in upright and supine positions. The expected duration of the entire TCD protocol is 30 minutes.

The TCD examination will be repeated only in the patients with MS (i.e. not in control subjects) 4 h after the oral intake of 62.5 mg bosentan (Tracleer®) (when peak plasma concentrations are expected). This is a purely academic study and Bosentan will be purchased through the hospital pharmacy. The most common side effect of daily treatment with bosentan is hepatotoxicity. Adverse reactions to one single dose are very unlikely. The primary aim is to investigate the potential of TCD to evaluate changes in the cerebral circulation between patients with MS and controls. Bosentan is not the object of investigation in this study but can be considered as a 'Non Investigational Medicinal Product' (N.I.M.P.). Patients with MS will receive the product to increase CBF, an effect which has already been demonstrated in an earlier perfusion-weighted MRI study.

Fifteen patients with relapsing-remitting or progressive MS and 15 healthy controls, matched for sex and age, will be included in this study. Sample size calculation is based on the number of inclusion in previous studies regarding cerebral hemodynamic parameters in MS (mostly between 10 and 30).

The statistical analyses will be conducted with Statistical Package for the Social Sciences (SPSS) software. Mann Whitney U or Wilcoxon signed rank tests will be used where appropriate.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Multiple Sclerosis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Patients with Multiple Sclerosis

One examination with TCD baseline and with NIRS baseline, and a second examination with TCD after bosentan administration and with NIRS after bosentan administration will be performed; The examination will be repeated only in the patients with MS (i.e. not in control subjects) 4 h after the oral intake of one tablet 62.5 mg bosentan (Tracleer®) (when peak plasma concentrations are expected).

Group Type EXPERIMENTAL

TCD baseline

Intervention Type DEVICE

Measurement of cerebral circulation parameters with transcranial doppler baseline.

This examination will be performed in patients with multiple sclerosis and in healthy controls.

TCD after bosentan administration

Intervention Type DEVICE

Measurement of cerebral circulation parameters with transcranial doppler after administration of one tablet tracleer (Bosentan) 62,5 mg per oral.

This examination will only be performed in patients with multiple sclerosis.

NIRS baseline

Intervention Type DEVICE

Measurement of frontal lobe oxygen saturation with near-infrared spectroscopy baseline.

This examination will be performed in patients with multiple sclerosis and in healthy controls.

NIRS after bosentan administration

Intervention Type DEVICE

Measurement of frontal lobe oxygen saturation with near-infrared spectroscopy after administration of one tablet tracleer (Bosentan) 62,5 mg per oral.

This examination will only be performed in patients with multiple sclerosis.

Healthy controls

Only one examination with TCD baseline and NIRS baseline will be performed, without administration of bosentan.

Group Type EXPERIMENTAL

TCD baseline

Intervention Type DEVICE

Measurement of cerebral circulation parameters with transcranial doppler baseline.

This examination will be performed in patients with multiple sclerosis and in healthy controls.

NIRS baseline

Intervention Type DEVICE

Measurement of frontal lobe oxygen saturation with near-infrared spectroscopy baseline.

This examination will be performed in patients with multiple sclerosis and in healthy controls.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

TCD baseline

Measurement of cerebral circulation parameters with transcranial doppler baseline.

This examination will be performed in patients with multiple sclerosis and in healthy controls.

Intervention Type DEVICE

TCD after bosentan administration

Measurement of cerebral circulation parameters with transcranial doppler after administration of one tablet tracleer (Bosentan) 62,5 mg per oral.

This examination will only be performed in patients with multiple sclerosis.

Intervention Type DEVICE

NIRS baseline

Measurement of frontal lobe oxygen saturation with near-infrared spectroscopy baseline.

This examination will be performed in patients with multiple sclerosis and in healthy controls.

Intervention Type DEVICE

NIRS after bosentan administration

Measurement of frontal lobe oxygen saturation with near-infrared spectroscopy after administration of one tablet tracleer (Bosentan) 62,5 mg per oral.

This examination will only be performed in patients with multiple sclerosis.

Intervention Type DEVICE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Transcranial doppler Transcranial doppler Tracleer Endothelin-1 receptor antagonist Near-infrared spectroscopy ForeSight Near-infrared Spectroscopy Endothelin-1 receptor antagonist Tracleer

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Patients with the diagnosis of relapsing-remitting, primary progressive of secondary progressive MS, according to the 2010 revised McDonald criteria.
* Written informed consent must be obtained.

Exclusion Criteria

* MS patients with a known contra-indication for bosentan: liver dysfunction, use of cyclosporine A, allergy.
* Pregnancy
* No evidence of MS relapse within the 3 months prior to inclusion.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Universitair Ziekenhuis Brussel

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Ilse AS Peeters, Student

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, Universitair Ziekenhuis (UZ) Brussel, Brussels. Belgium Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium

Miguel D'haeseleer, MD, PhD

Role: STUDY_CHAIR

Department of Neurology, Universitair Ziekenhuis (UZ) Brussel, Brussels. Belgium Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium

Jacques De Keyser, MD, PhD

Role: STUDY_DIRECTOR

Department of Neurology, Universitair Ziekenhuis (UZ) Brussel, Brussels. Belgium Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Department of Neurology, Universitair Ziekenhuis (UZ) Brussel. Center for Neurosciences, Vrije Universiteit Brussel

Jette, Vlaams-Brabant, Belgium

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Belgium

References

Explore related publications, articles, or registry entries linked to this study.

Law M, Saindane AM, Ge Y, Babb JS, Johnson G, Mannon LJ, Herbert J, Grossman RI. Microvascular abnormality in relapsing-remitting multiple sclerosis: perfusion MR imaging findings in normal-appearing white matter. Radiology. 2004 Jun;231(3):645-52. doi: 10.1148/radiol.2313030996.

Reference Type BACKGROUND
PMID: 15163806 (View on PubMed)

Adhya S, Johnson G, Herbert J, Jaggi H, Babb JS, Grossman RI, Inglese M. Pattern of hemodynamic impairment in multiple sclerosis: dynamic susceptibility contrast perfusion MR imaging at 3.0 T. Neuroimage. 2006 Dec;33(4):1029-35. doi: 10.1016/j.neuroimage.2006.08.008. Epub 2006 Sep 22.

Reference Type BACKGROUND
PMID: 16996280 (View on PubMed)

Varga AW, Johnson G, Babb JS, Herbert J, Grossman RI, Inglese M. White matter hemodynamic abnormalities precede sub-cortical gray matter changes in multiple sclerosis. J Neurol Sci. 2009 Jul 15;282(1-2):28-33. doi: 10.1016/j.jns.2008.12.036. Epub 2009 Jan 31.

Reference Type BACKGROUND
PMID: 19181347 (View on PubMed)

Saindane AM, Law M, Ge Y, Johnson G, Babb JS, Grossman RI. Correlation of diffusion tensor and dynamic perfusion MR imaging metrics in normal-appearing corpus callosum: support for primary hypoperfusion in multiple sclerosis. AJNR Am J Neuroradiol. 2007 Apr;28(4):767-72.

Reference Type BACKGROUND
PMID: 17416836 (View on PubMed)

D'haeseleer M, Beelen R, Fierens Y, Cambron M, Vanbinst AM, Verborgh C, Demey J, De Keyser J. Cerebral hypoperfusion in multiple sclerosis is reversible and mediated by endothelin-1. Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5654-8. doi: 10.1073/pnas.1222560110. Epub 2013 Mar 18.

Reference Type BACKGROUND
PMID: 23509249 (View on PubMed)

Compston A, Coles A. Multiple sclerosis. Lancet. 2008 Oct 25;372(9648):1502-17. doi: 10.1016/S0140-6736(08)61620-7.

Reference Type BACKGROUND
PMID: 18970977 (View on PubMed)

ElSankari S, Baledent O, van Pesch V, Sindic C, de Broqueville Q, Duprez T. Concomitant analysis of arterial, venous, and CSF flows using phase-contrast MRI: a quantitative comparison between MS patients and healthy controls. J Cereb Blood Flow Metab. 2013 Sep;33(9):1314-21. doi: 10.1038/jcbfm.2013.95. Epub 2013 Jun 19.

Reference Type BACKGROUND
PMID: 23778162 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

B.U.N. 1432101422450

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.